Harnessing Neurogenic Potential of Glial Cell Types as an Emerging Strategy for Treating Epilepsy

In every third case of epilepsy, anti-seizure drugs are ineffective, so the search for new therapies for this disease is ongoing. In recent years, new methods for generating cells with desired properties, as well as for the targeted expression of genes in specific cell types in situ within the brain, were designed. These methods allowed researchers to consider the idea of transforming resident glial cells into neurons in conditions like epilepsy; in such pathologies it may rescue both neuronal loss and gliosis. In this review, we describe epilepsy-associated pathological changes in glial cells, the neurogenic potential of different glial types (their similarities to neural stem cells and their inherent limited ability to produce neurons in response to brain damage), and existing methods of neuronal transdifferentiation starting with different cell types with varying proximity in lineage distance to neurons. Based on overlaps between these topics, we make conclusions about the applicability of glia-to-neuron conversion in treating epilepsy and the most important challenges that should be considered in designing experiments and clinical trials for this strategy.